The following statement updates all previous recommendations on
use of
immune globulins for protection against viral hepatitis (MMWR
1981;30:423-35)
and use of hepatitis B vaccine and hepatitis B immune globulin for
prophylaxis of hepatitis B (MMWR 1982;31:317-28 and MMWR
1984;33:285-90).

INTRODUCTION

The term "viral hepatitis" is commonly used for several
clinically
similar diseases that are etiologically and epidemiologically
distinct (1).
Two of these, hepatitis A (formerly called infectious hepatitis)
and
hepatitis B (formerly called serum hepatitis) have been recognized
as
separate entities since the early 1940s and can be diagnosed with
specific
serologic tests. The third, currently known as non-A, non-B
hepatitis, is
probably caused by at least two different agents, and lacking
specific
diagnostic tests, remains a disease diagnosed by exclusion. It is
an
important form of acute viral hepatitis in adults and currently
accounts for
most posttransfusion hepatitis in the United States. An epidemic
type of non-
A, non-B hepatitis, which is probably spread by the fecal-oral
route and is
different from the types seen in the United States, has been
described in
parts of Asia and North Africa (2).

A fourth type of hepatitis, delta hepatitis, has recently been
charac-
terized as an infection dependent on hepatitis B virus. It may
occur as a
coinfection with acute hepatitis B infection or as superinfection
of a
hepatitis B carrier (3).

HEPATITIS SURVEILLANCE

Approximately 21,500 cases of hepatitis A, 24,300 cases of
hepatitis B,
3,500 cases of non-A, non-B hepatitis, and 7,100 cases of hepatitis
type
unspecified were reported in the United States in 1983. Most cases
of each
type occur among young adults. Since reporting from many localities
is
incomplete, the actual number of hepatitis cases occurring annually
is
thought to be several times the reported number.

IMMUNE GLOBULINS

Immune globulins used in medical practice are sterile solutions
of anti-
bodies (immunoglobulins) from human plasma. They are prepared by
cold ethanol
fractionation of large plasma pools and contain 10%-18% protein. In
the
United States, plasma is primarily obtained from professional
donors. Only
plasma shown to be free of hepatitis B surface antigen (HBsAg) is
used to
prepare immune globulins.

Immune globulin (IG) (formerly called "immune serum globulin,"
ISG, or
"gamma globulin") produced in the United States contains antibodies
against
the hepatitis A virus (anti-HAV) and the hepatitis B surface
antigen (anti-
HBs). Tests of IG lots prepared since 1977 indicate that both types
of
antibody have uniformly been present. Hepatitis B immune globulin
(HBIG) is
an IG prepared from plasma containing high titers of anti-HBs.

Neither IG nor HBIG commercially available in the United States
transmits
hepatitis or other viral infections. There is no evidence that the
causative
agent of AIDS (human T-lymphotropic virus type
III/lymphadenopathy-associated
virus {HTLV-III/LAV}) has been transmitted by IG or HBIG (4).

Serious adverse effects from immune globulins administered as
recommended
have been exceedingly rare. Standard immune globulins are prepared
for
intramuscular use and should not be given intravenously. Two
preparations for
intravenous use in immunodeficient and other selected patients have
recently
become available in the United States but are not recommended for
hepatitis
prophylaxis. Immune globulins are not contraindicated for pregnant
women.

HEPATITIS A

Hepatitis A is caused by the hepatitis A virus (HAV), a 27-nm
ribonucleic
acid (RNA) agent that is a member of the picornavirus family. The
illness
caused by HAV characteristically has an abrupt onset with fever,
malaise,
anorexia, nausea, abdominal discomfort, and jaundice. Severity is
related to
age. In children, most infections are asymptomatic, and illness is
usually
not accompanied by jaundice. Most infected adults become
symptomatically ill
with jaundice. Fatality among reported cases is infrequent (about
0.6%).

Hepatitis A is primarily transmitted by person-to-person
contact,
generally through fecal contamination. Transmission is facilitated
by poor
personal hygiene, poor sanitation, and intimate (intrahousehold or
sexual)
contact. Common-source epidemics from contaminated food and water
also occur.
Sharing utensils or cigarettes or kissing are not believed to
transmit the
infection.

The incubation period of hepatitis A is 15-50 days (average
28-30). High
concentrations of HAV (10((8)) particles/g) are found in stools of
infected
persons. Fecal virus excretion reaches its highest concentration
late in the
incubation period and early in the prodromal phase of illness, and
diminishes
rapidly once jaundice appears. Greatest infectivity is during the
2-week
period immediately before the onset of jaundice. Viremia is of
short
duration; virus has not been found in urine or other body fluids. A
chronic
carrier state with HAV in blood or feces has not been demonstrated.
Trans-
mission of HAV by blood transfusion has occurred but is rare.

The diagnosis of acute hepatitis A is confirmed by finding
IgM-class
anti-HAV in serum collected during the acute or early convalescent
phase of
disease. IgG-class anti-HAV, which appears in the convalescent
phase of
disease and remains detectable in serum thereafter, apparently
confers
enduring protection against disease. Commercial tests are available
to detect
IgM anti-HAV and total anti-HAV in serum.

Although the incidence of hepatitis A in the United States has
decreased
over the last 15 years, it is still a common infection in older
children and
young adults. About 38% of reported hepatitis cases in this country
are
attributable to hepatitis A.

Recommendations for IG prophylaxis of hepatitis A. Numerous
field studies
conducted in the past 4 decades confirm that IG given before
exposure or
during the incubation period of hepatitis A is protective against
clinical
illness (5-7). Its prophylactic value is greatest (80%-90%) when
given early
in the incubation period and declines thereafter (7).

Preexposure prophylaxis. The major group for whom preexposure
prophylaxis
is recommended is international travelers. The risk of hepatitis A
for U.S.
citizens traveling abroad varies with living conditions, incidence
of
hepatitis A infection in areas visited, and length of stay (8,9).
In general,
travelers to developed areas of western Europe, Japan, and
Australia are at
no greater risk of infection than in the United States. In
contrast,
travelers to developing countries may be at significant risk of
infection. In
such areas, the best way to prevent hepatitis A and other enteric
diseases is
to avoid potentially contaminated water or food. Drinking water (or
beverages
with ice) of unknown purity and eating uncooked shellfish or
uncooked fruits
or vegetables that are not peeled (or prepared) by the traveler
should be
avoided.

IG is recommended for travelers to developing countries if they
will be
eating in settings of poor or uncertain sanitation (some
restaurants or
homes) or will be visiting extensively with local persons,
especially young
children, in settings with poor sanitary conditions. Persons who
plan to
reside in developing areas for long periods should receive IG
regularly if
they anticipate exposure as described above or will be living in
rural areas
with poor sanitation.

For such travelers, a single dose of IG of 0.02 ml/kg is
recommended if
travel is for less than 2 months. For prolonged travel, 0.06 ml/kg
should be
given every 5 months. For persons who require repeated IG
prophylaxis,
screening for total anti-HAV antibodies before travel may be useful
to define
susceptibility and eliminate unnecessary doses of IG in those who
are immune.

Postexposure prophylaxis. A serologic test for the diagnosis of
acute
hepatitis A is now widely available. Since only 38% of acute
hepatitis cases
in the United States result from hepatitis A, serologic
confirmation of
hepatitis A in the index case is recommended before treatment of
contacts.
Serologic screening of contacts for anti-HAV before giving IG is
not
recommended because screening is more costly than IG and would
delay its
administration.

IG should be given as soon as possible after exposure; giving
IG more
than 2 weeks after exposure is not indicated.

Specific recommendations for IG prophylaxis of hepatitis A
depend on the
nature of the HAV exposure:

Close personal contact. IG is recommended for all household
and sexual
contacts of persons with hepatitis A.

Day-care centers. Day-care facilities with children in
diapers can be
important settings for HAV transmission (10-12). IG should
be admin-
istered to all staff and attendees of day-care centers or
homes if:
(a) one or more hepatitis A cases are recognized among
children or
employees; or (b) cases are recognized in two or more
households of
center attendees. When an outbreak (hepatitis cases in three
or more
families) occurs, IG should also be considered for members
of house-
holds whose diapered children attend. In centers not
enrolling
children in diapers, IG need only be given to classroom
contacts of an
index case.

Schools. Contact at elementary and secondary schools is
usually not an
important means of transmitting hepatitis A. Routine
administration of
IG is not indicated for pupils and teachers in contact with
a patient.
However, when epidemiologic study clearly shows the
existence of a
school- or classroom-centered outbreak, IG may be given to
those who
have close personal contact with patients.

Institutions for custodial care. Living conditions in some
institu-
tions, such as prisons and facilities for the
developmentally
disabled, favor transmission of hepatitis A. When outbreaks
occur,
giving IG to residents and staff who have close contact with
patients
with hepatitis A may reduce the spread of disease. Depending
on the
epidemiologic circumstances, prophylaxis can be limited in
extent or
can involve the entire institution.

Hospitals. Routine IG prophylaxis for hospital personnel is
not indi-
cated. Rather, sound hygienic practices should be
emphasized. Staff
education should point out the risk of exposure to hepatitis
A and
emphasize precautions regarding direct contact with
potentially
infective materials (13).

Outbreaks of hepatitis A among hospital staff occur
occasionally,
usually in association with an unsuspected index patient who
is
fecally incontinent. Large outbreaks have occurred among
staff and
family contacts of infected infants in neonatal
intensive-care units.
In outbreaks, prophylaxis of persons exposed to feces of
infected
patients may be indicated.

Offices and factories. Routine IG administration is not
indicated
under the usual office or factory conditions for persons
exposed to a
fellow worker with hepatitis A. Experience shows that casual
contact
in the work setting does not result in virus transmission.

Common-source exposure. IG might be effective in preventing
foodborne
or waterborne hepatitis A if exposure is recognized in time.
However,
IG is not recommended for persons exposed to a common source
of hepa-
titis infection after cases have begun to occur in those
exposed,
since the 2-week period during which IG is effective will
have been
exceeded.

If a foodhandler is diagnosed as having hepatitis A,
common-source
transmission is possible but uncommon. IG should be
administered to
other foodhandlers but is usually not recommended for
patrons.
However, IG administration to patrons may be considered if
(a) the
infected person is directly involved in handling, without
gloves,
foods that will not be cooked before they are eaten; (b) the
hygienic
practices of the foodhandler are deficient; and (c) patrons
can be
identified and treated within 2 weeks of exposure.
Situations where
repeated exposures may have occurred, such as in
institutional cafete-
rias, may warrant stronger consideration of IG use.

For postexposure IG prophylaxis, a single intramuscular
dose of
0.02 ml/kg is recommended.

HEPATITIS B

Hepatitis B virus (HBV) infection is a major cause of acute and
chronic
hepatitis, cirrhosis, and primary hepatocellular carcinoma
worldwide. The
frequency of HBV infection and patterns of transmission vary
markedly in
different parts of the world. In the United States, western Europe,
and
Australia, it is a disease of low endemicity, with only 0.1%-0.5%
of the
population being virus carriers and infection occurring primarily
during
adulthood. In contrast, HBV infection is highly endemic in China
and
Southeast Asia, sub-Saharan Africa, most Pacific islands, and the
Amazon
Basin; in these areas, 5%-15% of the population carry the virus,
and most
persons acquire infection at birth or during childhood. In other
parts of the
world, HBV is moderately endemic, and 1%-4% of persons are HBV
carriers.
Recommendations for prophylaxis of hepatitis B will vary in
accordance with
local patterns of HBV transmission. The recommendations that follow
are
intended for use in the United States.

Hepatitis B infection is caused by the HBV, a 42-nm,
double-shelled
deoxyribonucleic acid (DNA) virus. Several well-defined
antigen-antibody
systems have been associated with HBV infection (Table 1). HBsAg,
formerly
called "Australia antigen" or "hepatitis-associated antigen," is
found on the
surface of the virus and on accompanying 22-nm spherical and
tubular forms.
HBsAg can be identified in serum 30-60 days after exposure to HBV
and
persists for variable periods. The various subtypes (adr, adw, ayw,
ayr) of
HBsAg provide useful epidemiologic markers. Antibody against HBsAg
(anti-HBs)
develops after a resolved infection and is responsible for
long-term
immunity. Anti-HBc, the antibody to the core antigen (an internal
component
of the virus), develops in all HBV infections and persists
indefinitely. IgM
anti-HBc appears early in infection and persists for 6 or more
months; it is
a reliable marker of acute or recent HBV infection. The hepatitis B
e antigen
(HBeAg) is a third antigen, presence of which correlates with HBV
replication
and high infectivity. Antibody to HBeAg (anti-HBe) develops in most
HBV
infections and correlates with lower infectivity.

The onset of acute hepatitis B is generally insidious. Clinical
symptoms
and signs include various combinations of anorexia, malaise,
nausea,
vomiting, abdominal pain, and jaundice. Skin rashes, arthralgias,
and
arthritis can also occur. Overall fatality rates for reported cases
generally
do not exceed 2%. The incubation period of hepatitis B is
long--45-160 days
(average 60-120).

HBV infection in the United States. The estimated lifetime risk
of HBV
infection in the United States varies from almost 100% for the
highest-risk
groups to approximately 5% for the population as a whole. An
estimated
200,000 persons, primarily young adults, are infected each year.
One-quarter
become ill with jaundice; more than 10,000 patients require
hospitalization;
and an average of 250 die of fulminant disease each year. Between
6% and 10%
of young adults with HBV infection become carriers. The United
States
currently contains an estimated pool of 500,000-1,000,000
infectious
carriers. Chronic active hepatitis develops in over 25% of carriers
and often
progresses to cirrhosis. Furthermore, HBV carriers have a risk of
developing
primary liver cancer that is 12-300 times higher than that of other
persons.
It is estimated that 4,000 persons die from hepatitis B-related
cirrhosis
each year in this country and that more than 800 die from hepatitis
B-related
liver cancer.

The role of the HBV carrier is central in the epidemiology of
HBV
transmission. A carrier is defined as a person who is
HBsAg-positive on at
least two occasions at least 6 months apart. Although the degree of
infectivity is best correlated with HBeAg-positivity, any person
positive for
HBsAg is potentially infectious. The likelihood of developing the
carrier
state varies inversely with the age at which infection occurs.
During the
perinatal period, HBV transmitted from HBeAg-positive mothers
results in HBV
carriage in up to 90% of infected infants, whereas 6%-10% of
acutely infected
adults become carriers.

Carriers and persons with acute infection have highest
concentrations of
HBV in the blood and serous fluids; less is present in other body
fluids,
such as saliva and semen. Transmission occurs via percutaneous or
permucosal
routes. Infective blood or body fluids can be introduced by
contaminated
needles or through sexual contact. Infection can occur in settings
of
continuous close personal contact, such as in households or among
children in
institutions for the mentally retarded, presumably via inapparent
or
unnoticed contact of infectious secretions with skin lesions or
mucosal
surfaces. Transmission of infection by transfusion of contaminated
blood or
blood products has been greatly reduced since the advent of routine
screening
with highly sensitive tests for HBsAg. HBV is not transmitted via
the fecal-
oral route or by contamination of food or water.

Serologic surveys demonstrate that, although HBV infection is
uncommon
among adults in the general population, it is highly prevalent in
certain
groups. Those at risk, based on the prevalence of serologic markers
of
infection, are described in Table 2. Immigrants/refugees and their
descendants from areas of high HBV endemicity are at high risk of
acquiring
HBV infection. Homosexually active men and users of illicit
injectable drugs
are among the highest-risk groups, acquiring infection soon after
adopting
these lifestyles (10%-20%/year). Inmates of prisons have high
prevalence of
HBV markers usually because of prior parenteral drug abuse; actual
risk of
transmission in prisons is also associated with parenteral drug
abuse in
prisons. Patients and staff in custodial institutions for the
mentally
retarded are also at increased risk of having HBV infection.
Classroom
contacts, particularly teachers or instructors, of some
deinstitutionalized
carriers may also be at higher risk than the general population.
Household
contacts and sexual partners of HBV carriers are at increased risk,
as are
hemodialysis patients and recipients of certain pooled plasma
products.

There is increased risk for medical and dental workers and
related
laboratory and support personnel who have contact with blood.
Employment in
a hospital without exposure to blood carries no greater risk than
that for
the general population.

Hepatitis B prophylaxis. Two types of products are available
for
prophylaxis against hepatitis B. Hepatitis B vaccine, licensed in
1981,
provides active immunization against HBV infection. and its use is
recom-
mended for both pre- and postexposure prophylaxis. IG products
provide
temporary, passive protection and are indicated only in certain
postexposure
settings.

IG and HBIG. IG and HBIG contain different amounts of anti-HBs.
IG is
prepared from plasma that is not preselected for anti-HBs content.
Since
1977, all lots tested have contained anti-HBs at a titer of at
least 1:100 by
radioimmunoassay (RIA). HBIG is prepared from plasma preselected
for high-
titer anti-HBs. In the United States, HBIG has an anti-HBs titer of
higher
than 1:100,000 by RIA. There is no evidence that the causative
agent of AIDS
(HTLV-III/LAV) has been transmitted by IG or HBIG (4).

Hepatitis B vaccine. Hepatitis B vaccine licensed in the United
States is
a suspension of inactivated, alum-adsorbed 22-nm surface antigen
particles
that have been purified from human plasma by a combination of
biophysical
(ultracentrifugation) and biochemical procedures. Inactivation is a
threefold
process using 8M urea, pepsin at pH 2, and 1:4000 formalin. These
treatment
steps have been shown to inactivate representatives of all classes
of viruses
found in human blood, including the causative agent of AIDS
(HTLV-III/LAV)
(14). HB vaccine contains 20 ug/ml of HBsAg protein.

After a series of three intramuscular doses of hepatitis B
vaccine, over
90% of healthy adults develop protective antibody (15,16). A course
of three
10-ug doses induces antibody in virtually all infants and children
from birth
through 9 years of age. The deltoid (arm) is the recommended site
for
hepatitis B vaccination in adults; immunogenicity of vaccine in
adults is
significantly lower when injections are given in the buttock (81%)
(17). The
immunogenicity of the intradermal route has not yet been clearly
established.

Field trials of the U.S.-manufactured vaccine have shown
80%-95% efficacy
in preventing infection or hepatitis among susceptible persons
(16,18).
Protection against illness is virtually complete for persons who
develop
adequate antibody levels* after vaccination. The duration of
protection and
need for booster doses are not yet defined. However, only 10%-15%
of persons
who develop adequate antibody after three vaccine doses will lose
antibody
within 4 years, and among those who lose antibody, protection
against viremic
infection and liver inflammation appears to persist. Immunogenicity
and
efficacy of the licensed vaccine in hemodialysis patients is much
lower than
in normal adults; protection may last only as long as adequate
antibody
levels persist (19).

Vaccine usage. Primary vaccination consists of three
intramuscular doses
of vaccine, with the second and third doses given 1 and 6 months,
respec-
tively, after the first. Adults and older children should be given
20 ug (1.0
ml) per dose, while children under 10 years should receive 10 ug
(0.5 ml) per
dose. For patients undergoing hemodialysis and for other
immunosuppressed
patients, a 40-ug (2.0-ml) dose should be used. Vaccine doses
administered at
longer intervals provide equally satisfactory protection, but
optimal protec-
tion is not conferred until after the third dose. Hepatitis B
vaccine should
only be given in the deltoid muscle in adults and children or in
the antero-
lateral thigh muscle in infants and neonates. Since hepatitis B
vaccine is an
inactivated (noninfective) product, it is presumed that there will
be no
interference with other simultaneously administered vaccines.

Data are not available on the safety of the vaccine for the
developing
fetus. Because the vaccine contains only noninfectious HBsAg
particles, there
should be no risk to the fetus. In contrast, HBV infection in a
pregnant
woman may result in severe disease for the mother and chronic
infection for
the newborn. Pregnancy should not be considered a contraindication
to the use
of this vaccine for persons who are otherwise eligible.

Vaccine storage. Vaccine should be stored at 2 C-8 C (36 F-46
F) but not
frozen. Freezing destroys the potency of the vaccine.

Side effects and adverse reactions. The most common side effect
observed
in prevaccination trials was soreness at the injection site. Among
an
estimated 750,000 vaccinees, approximately 100 episodes of severe
illness
have been reported after receipt of vaccine. These have included
arthralgias,
neurologic reactions (such as Guillain-Barre syndrome), and other
illnesses.
The rate of Guillain-Barre syndrome following HB vaccine does not
appear to
be significantly increased above that observed in normal adults.
Such
temporally associated illnesses are not considered to be
etiologically
related to hepatitis B vaccine.

Effect of vaccination on carriers and immune persons. The
vaccine
produces neither therapeutic nor adverse effects in HBV carriers
(20).
Vaccination of individuals who possess anti-bodies against HBV from
a
previous infection is not necessary but will not cause adverse
effects. Such
individuals will have a postvaccination increase in their anti-HBs
levels.
Passively acquired antibody, whether from HBIG or IG administration
or from
the transplacental route, will not interfere with active
immunization (21).

Prevaccination serologic screening for susceptibility. The
decision to
screen potential vaccine recipients for prior infection depends on
three
variables: (1) the cost of vaccination; (2) the cost of testing for
suscep-
tibility; and (3) the expected prevalence of immune individuals in
the group.
Figure 1 shows the relative cost-effectiveness of screening, given
different
costs of screening tests and the expected prevalence of immunity.
In
constructing the figure, the assumption was made that the cost of
three doses
of vaccine is $100 and that there are additional costs for
administration.
For any combination of screening costs and immunity to hepatitis,
the cost-
effectiveness can be estimated. For example, if the expected
prevalence of
serologic markers for HBV is over 20%, screening is cost-effective
if costs
of screening are no greater than $30 per person. If the expected
prevalence
of markers is less than 8%, and if the costs of screening are
greater than
$10 per person, vaccination without screening is cost-effective.

Screening in groups with the highest risk of HBV infection
(Table 2) will
be cost-effective unless testing costs are extremely high. For
groups at
intermediate risk, cost-effectiveness of screening may be marginal,
and
vaccination programs may or may not utilize screening. For groups
with a low
expected prevalence of HBV serologic markers, such as health
professionals in
their training years, screening will not be cost-effective.

For routine screening, only one antibody test, either anti-HBc
or anti-
HBs, need be used. Anti-HBc will identify all previously infected
persons,
both carriers and noncarriers, but will not discriminate between
members of
the two groups. Anti-HBs will identify those previously infected,
except
carriers. For groups expected to have carrier rates of under 2%,
such as
health-care workers, neither test has a particular advantage. For
groups with
higher carrier rates, anti-HBc may be preferred to avoid
unnecessary vaccin-
ation of carriers. If the RIA anti-HBs test is used for screening,
a minimum
of 10 RIA sample ratio units should be used to designate immunity
(2.1 is the
usual designation of a positive test). If enzyme immunoassay (EIA)
is used,
the manufacturers' recommended positive is appropriate.

Serologic confirmation of postvaccination immunity and
revaccination of
nonresponders. When given in the deltoid, hepatitis B vaccine
produces
protective antibody (anti-HBs)in more than 90% of healthy persons.
Testing
for immunity following vaccination is not recommended routinely but
is
advised for persons whose subsequent management depends on knowing
their
immune status, such as dialysis patients and staff, and for persons
in whom
a suboptimal response may be anticipated, such as those who have
received
vaccine in the buttock.

Revaccination of persons who do not respond to primary series
(nonre-
sponders) produces adequate antibody in only one-third when the
primary
vaccination has been given in the deltoid. Therefore, revaccination
of
nonresponders to deltoid injection is not recommended routinely.
For persons
who did not respond to a primary vaccine series given in the
buttock, prelim-
inary data from two small studies suggest that revaccination in the
arm
induces adequate antibody in over 75%. Revaccination should be
strongly
considered for such persons.

Preexposure vaccination. Persons at substantial risk of
acquiring HBV
infection who are demonstrated or judged likely to be susceptible
should be
vaccinated. They include:

Health-care workers. The risk of health-care workers
acquiring HBV
infection depends on the frequency of exposure to blood or
blood
products and on the frequency of needlesticks. These risks
vary
during the training and working career of each individual
but are
often highest during the professional training period. For
this
reason, it is recommended that vaccination be completed
during
training in schools of medicine, dentistry, nursing,
laboratory
technology, and other allied health professions.

The risk of HBV infection for hospital personnel can
vary both
among hospitals and within hospitals. In developing
specific immuni-
zation strategies, hospitals should use available published
data
about the risk of infection (22-24) and may wish to
evaluate their
own clinical and institutional experience with hepatitis B.
Studies
in urban centers have indicated that occupational groups
with
frequent exposure to blood and/or needles have the highest
risk of
acquiring HBV infection, including (but not limited to) the
following
groups: medical technologists, operating room staff,
phlebotomists
and intravenous therapy nurses, surgeons and pathologists,
and
oncology and dialysis unit staff. Groups shown to be at
increased
risk in some hospitals include: emergency room staff,
nursing
personnel, and staff physicians.

Other health-care workers based outside hospitals who
have
frequent contact with blood or blood products are also at
increased
risk of acquiring HBV infection. These include (but are not
limited
to): dental professionals (dentists, oral surgeons, dental
hygienists), laboratory and blood bank technicians,
dialysis center
staff, emergency medical technicians, and morticians.

Clients and staff of institutions for the mentally
retarded. Suscep-
tible clients and staff who work closely with clients of
institutions
for the mentally retarded should be vaccinated. Risks for
staff are
comparable to those for health-care personnel in other
high-risk
environments. However, the risk in institutional
environments is
associated, not only with blood exposure, but also with
bites and
contact with skin lesions and other infective secretions.
Susceptible
clients and staff who live or work in smaller (group)
residential
settings with known HBV carriers should also receive
hepatitis B
vaccine.

Hemodialysis patients. Numerous studies have established
the high
risk of HBV transmission in hemodialysis units. Although
recent data
have shown not only a decrease in the rate of HBV infection
in hemo-
dialysis units but also a lower vaccine efficacy in these
patients,
vaccination is recommended for susceptible patients.
Environmental
control measures and regular serologic screening (based on
immune
status) of patients should be maintained.

Homosexually active men. Susceptible homosexually active
men should
be vaccinated regardless of their ages or duration of their
homo-
sexual practices. It is important to vaccinate persons as
soon as
possible after their homosexual activity begins.
Homosexually active
women are not at increased risk of sexually transmitted HBV
infection.

Users of illicit injectable drugs. All users of illicit
injectable
drugs who are susceptible to HBV should be vaccinated as
early as
possible after their drug use begins.

Recipients of certain blood products. Patients with
clotting
disorders who receive clotting factor concentrates have an
elevated
risk of acquiring HBV infection. Vaccination is recommended
for these
persons and should be initiated at the time their specific
clotting
disorder is identified. Screening is recommended for
patients who
have already received multiple infusions of these products.

Household and sexual contacts of HBV carriers. Household
contacts of
HBV carriers are at high risk of acquiring HBV infection.
Sexual
contacts appear to be at greatest risk. When HBV carriers
are identi-
fied through routine screening of donated blood, diagnostic
testing
in hospitals, prenatal screening, screening of refugees, or
other
screening programs, they should be notified of their status
and their
susceptible household contacts vaccinated.

Families accepting orphans or unaccompanied minors from
countries
of high HBV endemicity should have the child screened for
HBsAg, and
if positive, family members should be vaccinated.

Other contacts of HBV carriers. Persons in casual contact
with
carriers at schools, offices, etc., are at minimal risk of
acquiring
HBV infection, and vaccine is not routinely recommended for
them.
However, classroom contacts of deinstitutionalized mentally
retarded HBV carriers who behave aggressively or have
special medical
problems that increase the risk of exposure to their blood
or serous
secretions may be at risk. In such situations, vaccine may
be offered
to classroom contacts.

Special high-risk populations. Some American populations,
such as
Alaskan Eskimos, native Pacific islanders, and immigrants
and
refugees from areas with highly endemic disease
(particularly eastern
Asia and sub-Saharan Africa) have high HBV infection rates.
Depending
on specific epidemiologic and public health considerations,
more
extensive vaccination programs should be considered.

Inmates of long-term correctional facilities. The prison
environment
may provide a favorable setting for the transmission of HBV
because
of the frequent use of illicit injectable drugs and
homosexual
practices. Moreover, it provides an access point for
vaccination of
parenteral drug abusers. Prison officials should consider
undertaking
screening and vaccination programs directed at those who
abuse drugs
before or while in prison.

Heterosexually active persons. Heterosexually active
persons with
multiple sexual partners are at increased risk of acquiring
HBV
infection; risk increases with increasing sexual activity.
Vaccin-
ation should be considered for persons who present for
treatment of
sexually transmitted diseases and who have histories of
sexual
activity with multiple partners.

International travelers. Vaccination should be considered
for persons
who plan to reside more than 6 months in areas with high
levels of
endemic HBV and who will have close contact with the local
popula-
tion. Vaccination should also be considered for short-term
travelers
who are likely to have contact with blood from or sexual
contact with
residents of areas with high levels of endemic disease.
Hepatitis B
vaccination of travelers ideally should begin 6 months
before travel
in order to complete the full vaccine series; however, a
partial
series will offer some protection against HBV infection.

Postexposure prophylaxis for hepatitis B. Prophylactic
treatment to
prevent hepatitis B infection after exposure to HBV should be
considered in
the following situations: perinatal exposure of an infant born to
an HBsAg-
positive mother; accidental percutaneous or permucosal exposure to
HBsAg-
positive blood; or sexual exposure to an HBsAg-positive person.

Recent studies have established the relative efficacies of
immune
globulins and/or hepatitis B vaccine in various exposure
situations. For
perinatal exposure to an HBsAg-positive, HBeAg-positive mother, a
regimen
combining one dose of HBIG at birth with the hepatitis B vaccine
series
started soon after birth is 85%-90% effective in preventing
development of
the HBV carrier state (25,27). Regimens involving either multiple
doses of
HBIG alone, or the vaccine series alone, have 70%-75% efficacy,
while a
single dose of HBIG alone has only 50% efficacy (28).

For accidental percutaneous exposure or sexual exposure, only
regimens
including HBIG and/or IG have been studied. A regimen of two HBIG
doses, one
given after exposure and one a month later, is about 75% effective
in
preventing hepatitis B following percutaneous exposure; a single
dose of HBIG
has similar efficacy when used following sexual exposure (29-31).
IG may have
some effect in preventing clinical hepatitis B following
percutaneous
exposures and can be considered as an alternative to HBIG when it
is not
possible to obtain HBIG.

Recommendations on postexposure prophylaxis are based on the
efficacy
data discussed above and on the likelihood of future HBV exposure
of the
person requiring treatment. In perinatal exposure and percutaneous
exposure
of high-risk health-care personnel, a regimen combining HBIG with
hepatitis
B vaccine will provide both short- and long-term protection, will
be less
costly than the two-dose HBIG treatment alone, and is the treatment
of
choice.

Perinatal exposure. One of the most efficient modes of HBV
transmission
is from mother to infant during birth. If the mother is positive
for both
HBsAg and HBeAg, about 70%-90% of infants will become infected, and
up to 90%
of these infected infants will become HBV carriers. If the
HBsAg-positive
carrier mother is HBeAg-negative, or if anti-HBe is present,
transmission
occurs less frequently and rarely leads to the HBV carrier state.
However,
severe acute disease, including fatal fulminant hepatitis in the
neonate, has
been reported (32,33). Prophylaxis of infants from all
HBsAg-positive mothers
is recommended, regardless of the mother's HBeAg or anti-HBe
status.

The efficacy of a combination of HBIG plus the hepatitis B
vaccine series
has been confirmed in recent studies. Although the following
regimen is
recommended (Table 3), other schedules have also been effective
(25-27,34).
The major consideration for all these regimens is the need to give
HBIG as
soon as possible after delivery.

HBIG (0.5 ml {10 ug}) should be administered intramuscularly
after
physiologic stabilization of the infant and preferably within 12
hours of
birth. Hepatitis B vaccine should be administered intramuscularly
in three
doses of 0.5 ml (10 ug) each. The first dose should be given
concurrently
with HBIG but at a different site. If vaccine is not available at
birth, the
first vaccine dose may be given within 7 days of birth. The second
and third
doses should be given 1 month and 6 months, respectively, after the
first.
Testing for HBsAg and anti-HBs is recommended at 12-15 months to
monitor the
final success or failure of therapy. If HBsAg is not detectable,
and anti-HBs
is present, the child has been protected. Testing for anti-HBc is
not useful,
since maternal anti-HBc may persist for more than 1 year; the
utility of
testing for IgM anti-HBc is currently being evaluated. HBIG
administered at
birth should not interfere with oral polio and
diphtheria-tetanus-pertussis
vaccines administered at 2 months of age.

Maternal screening. Since efficacy of the treatment regimen
depends on
administering HBIG on the day of birth, it is vital that
HBsAg-positive
mothers be identified before delivery. Mothers belonging to groups
known to
be at high risk of acquiring HBV infection (Table 4) should be
tested
routinely for HBsAg during a prenatal visit. If a mother belonging
to a high-
risk group has not been screened prenatally, HBsAg screening should
be done
at the time of delivery, or as soon as possible thereafter, and the
infant
treated as above if the mother is HBsAg-positive. If the mother is
identified
as HBsAg-positive more than 1 month after giving birth, the infant
should be
screened for HBsAg, and if negative, treated with hepatitis B
vaccine and
HBIG.

The appropriate obstetric and pediatric staff should be
notified directly
of HBsAg-positive mothers, so the staff may take appropriate
precautions to
protect themselves and other patients from infectious material,
blood, and
secretions, and so the neonate may receive therapy without delay
after birth.

Acute exposure to blood that contains (or might contain) HBsAg.
For
accidental percutaneous or permucosal exposure to blood that is
known to
contain or might contain HBsAg, the decision to provide prophylaxis
must take
into account several factors: (1) the hepatitis B vaccination
status of the
exposed person; (2) whether the source of blood is known or
unknown; and (3)
whether the HBsAg status of the source is known or unknown. Such
exposures
usually occur in persons who are candidates for hepatitis B
vaccine; for any
exposure in a person not previously vaccinated, hepatitis B
vaccination is
recommended.

The following outline and table summarize prophylaxis for
percutaneous
(needlestick or bite), ocular, or mucous-membrane exposure to blood
according
to the source of exposure and vaccination status of the exposed
person (Table
5). For greatest effectiveness, passive prophylaxis with HBIG (or
IG) should
be given as soon as possible after exposure (its value beyond 7
days of
exposure is unclear).

Exposed person not previously vaccinated. Hepatitis B
vaccination
should be considered the treatment of choice. Depending on
the source
of the exposure, HBsAg testing of the source and additional
prophy-
laxis of the exposed person may be warranted (see below).
Screening
the exposed person for immunity should be considered if such
screening
is cost-effective (as discussed in preexposure prophylaxis)
and if
this will not delay treatment beyond 7 days.

Source known HBsAg-positive. A single dose of HBIG (0.06
ml/kg)
should be given as soon as possible after exposure and
within 24
hours, if possible. The first dose of hepatitis B vaccine
(20 ug)
should be given intramuscularly at a separate site within
7 days of
exposure, and the second and third doses given 1 month
and 6 months
later (Table 5).** If HBIG cannot be obtained, IG in an
equivalent
dosage (0.06 ml/kg) may provide some benefit.

Source known, HBsAg status unknown. The following
guidelines are
suggested based on the relative probability that the
source is
HBsAg-positive and on the consequent risk of HBV
transmission:
(1) High risk that the source is HBsAg-positive, such as
patients

with a high risk of HBV carriage (Table 2) or
patients with
acute or chronic liver disease (serologically
undiagnosed). The
exposed person should be given the first dose of
hepatitis B
vaccine (20 ug) within 1 week of exposure and
vaccination
completed as recommended. The source person should be
tested
for HBsAg. If positive, the exposed person should be
given HBIG
(0.06 ml/kg) if within 7 days of exposure.
(2) Low risk that the source is positive for HBsAg. The
exposed

person should be given the first dose of hepatitis B
vaccine
(20 ug) within 1 week of exposure and vaccination
completed as
recommended. Testing of the source person is not
necessary.

Source unknown. The exposed person should be given the
first dose
of hepatitis B vaccine (20 ug) within 7 days of exposure
and
vaccination completed as recommended.

Exposed person previously vaccinated against hepatitis B.
For percu-
taneous exposures to blood in persons who have previously
received one
or more doses of hepatitis B vaccine, the decision to
provide addi-
tional prophylaxis will depend on the source of exposure and
on
whether the vaccinated person has developed anti-HBs
following vacci-
nation.

Source known HBsAg-positive. The exposed person should be
tested
for anti-HBs unless he/she has been tested within the
last 12
months. If the exposed person has adequate*** antibody,
no addi-
tional treatment is indicated.
(1) If the exposed person has not completed vaccination
and has

inadequate levels of antibody, one dose of HBIG (0.06
ml/kg)
should be given immediately and vaccination completed
as
scheduled.
(2) If the exposed person has inadequate antibody on
testing or has

previously not responded to vaccine, one dose of HBIG
should be
given immediately and a booster dose of vaccine (1 ml
or 20 ug)
given at a different site.
(3) If the exposed person shows inadequate antibody on
testing but

is known to have had adequate antibody in the past, a
booster
dose of hepatitis B vaccine (1 ml or 20 ug) should be
given.

laxis is necessary only if the exposed person is a
known
vaccine nonresponder. In this circumstance, the
source should
be tested for HBsAg and, if positive, the exposed
person
treated with one dose of HBIG (0.06 ml/kg)
immediately and a
booster dose of vaccine (1 ml or 20 ug) at a
different site. In
other circumstances, screening of the source for
HBsAg and the
exposed person for anti-HBs is not routinely
recommended,
because the actual risk of HBV infection is very low
(less than
1 per 1,000).****
(2) Low risk that the source is HBsAg-positive. The risk
of HBV

infection is minimal. Neither testing of the source
for HBsAg,
nor testing of the exposed person for anti-HBs, is
recommended.

Source unknown. The risk of HBV infection is minimal. No
treatment
is indicated.

HBsAg-positive persons are at increased risk of acquiring HBV
infection, and
HBIG has been shown to be 75% effective in preventing such
infections (31).
Because data are limited, the period after sexual exposure during
which HBIG
is effective is unknown, but extrapolation from other settings
makes it
unlikely that this period would exceed 14 days. Prescreening sexual
partners
for susceptibility before treatment is recommended if it does not
delay
treatment beyond 14 days after last exposure. Testing for anti-HBc
is the
most efficient prescreening test to use in this population group.

A single dose of HBIG (0.06 ml/kg) is recommended for
susceptible indi-
viduals who have had sexual contact with an HBsAg-positive person,
if HBIG
can be given within 14 days of the last sexual contact, and for
persons who
will continue to have sexual contact with an individual with acute
hepatitis
B before loss of HBsAg in that individual. In exposures between
hetero-
sexuals, hepatitis B vaccination may be initiated at the same time
as HBIG
prophylaxis; such treatment may improve efficacy of postexposure
treatment.
However, since 90% of persons with acute HBV infection become
HBsAg-negative
within 15 weeks of diagnosis, the potential for repeated exposure
to HBV is
limited. Hepatitis B vaccine is, therefore, optional in initial
treatment for
such exposures. If vaccine is not given, a second dose of HBIG
should be
given if the index patient remains HBsAg-positive for 3 months
after
detection. If the index patient is a known carrier or remains
positive for 6
months, hepatitis B vaccine should be offered to regular sexual
contacts. For
exposures among homosexual men, the hepatitis B vaccine series
should be
initiated at the time HBIG is given, since hepatitis B vaccine is
recommended
for all susceptible homosexual men. Additional doses of HBIG are
unnecessary
if vaccine is given. IG is an alternative to HBIG when it is not
possible to
obtain HBIG.

Household contacts of persons with acute HBV infection.
Prophylaxis for
other household contacts of persons with acute HBV infection is not
indicated
unless they have had identifiable blood exposure to the index case,
such as
by sharing toothbrushes or razors. Such exposures should be treated
similarly
to sexual exposures. If the index patient becomes a hepatitis B
carrier, all
household contacts should be given hepatitis B vaccine.

DELTA HEPATITIS

The delta virus (also known as hepatitis D virus {HDV} by some
investi-
gators) is a defective virus that may only cause infection in the
presence of
active HBV infection. The delta virus has been characterized as a
particle of
35-37 nm in size, consisting of RNA (mw 500,000) as genetic
material and an
internal protein antigen (delta-antigen), coated with HBsAg as the
surface
protein (3). Infection may occur as either coinfection with
hepatitis B or
superinfection of a hepatitis B carrier, each of which usually
cause an
episode of acute hepatitis. Coinfection usually resolves, while
superin-
fection frequently causes chronic delta infection and chronic
active
hepatitis. Both types of infection may cause fulminant hepatitis.

Delta infection may be diagnosed by detection of delta-antigen
in serum
during early infection and by the appearance of delta antibody
during or
after infection. Routes of delta transmission appear to be similar
to those
of hepatitis B. In the United States, delta infection occurs most
commonly
among persons at high risk of acquiring HBV infection, such as drug
addicts
and hemophilia patients.

A test for detection of delta antibody is expected to be
commercially
available soon. Other tests (delta antigen, IgM anti-delta) are
available
only in research laboratories.

Since the delta virus is dependent on hepatitis B for
replication,
prevention of hepatitis B infection, either preexposure or
postexposure, will
suffice to prevent delta infection in a person susceptible to
hepatitis B.
Known episodes of perinatal, sexual, or percutaneous exposure to
sera or
persons positive for both HBV and delta virus should be treated
exactly as
such exposures to hepatitis B alone.

Persons who are HBsAg carriers are at risk of delta infection,
especially
if they participate in activities that put them at high risk of
repeated
exposure to hepatitis B (parenteral drug abuse, homosexuality).
However, at
present there are no products available that might prevent delta
infection in
HBsAg carriers either before or after exposure.

NON-A, NON-B HEPATITIS

United States. Non-A, non-B hepatitis that presently occurs in
the United
States has epidemiologic characteristics similar to those of
hepatitis B,
occurring most commonly following blood transfusion and parenteral
drug
abuse. Multiple episodes of non-A, non-B hepatitis have been
observed in the
same individuals and may be due to different agents. Chronic
hepatitis
following acute non-A, non-B hepatitis infection varies in
frequency from 20%
to 70%. Experimental studies in chimpanzees have confirmed the
existence of
a carrier state, which may be present in up to 8% of the
population.

Although several studies have attempted to assess the value of
prophy-
laxis with IG against non-A, non-B hepatitis, the results have been
equivocal, and no specific recommendations can be made (35,36).
However, for
persons with percutaneous exposure to blood from a patient with
non-A, non-B
hepatitis, it may be reasonable to administer IG (0.06 ml/kg) as
soon as
possible after exposure.

Epidemic (fecal-oral) non-A, non-B hepatitis. In recent years,
epidemics
of non-A, non-B hepatitis spread by water or close personal contact
have been
reported from several areas of Southeast Asia (Indian subcontinent,
Burma)
and north Africa (2). Such epidemics generally affect adults and
cause
unusually high mortality in pregnant women. The disease has been
transmitted
to experimental animals, and candidate viruses have been
identified; however,
no serologic tests have yet been developed (37).

Epidemic non-A, non-B hepatitis has not been recognized in the
United
States or western Europe, and it is unknown whether the causative
agent is
present in these areas.

Travelers to areas having epidemic non-A, non-B hepatitis may
be at some
risk of acquiring this disease by close contact or by contaminated
food or
water. The value of IG in preventing this infection is unknown. The
best
prevention of infection is to avoid potentially contaminated food
or water,
as with hepatitis A and other enteric infections.

Adequate antibody is 10 or more sample ratio units (SRU) by
RIA or

positive by enzyme immunoassay.

** For persons who are not given hepatitis B vaccine, a second
dose of HBIG
should be given 1 month after the first dose.

*** Adequate antibody is 10 SRU or more by RIA or positive by EIA.
**** Estimated by multiplying the risk of vaccine nonresponse in
the exposed
person (.10) by the risk of the needle source being HBsAg-positive
(.05) by
the risk of HBV infection in a susceptible person having an
HBsAg-positive
needle-stick injury (.20).

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